The Influence of Vitamin D Status on the Severity of SARS-CoV-2 Respiratory Infection

Silva, José Diogo; Rouxinol-Dias, Ana; Rocha, Gustavo Melo; Correia, Sara; Almeida, Lúcia; Alves, Helena; Oliveira, Maria João

Introduction: The high prevalence of vitamin D (vitD) deficiency in the general population is well recognized. Evidence suggests an immunomodulatory role for vitD in pro-inflammatory conditions, but doubt remains on its association with the severity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) respiratory infection (RI). Aim: To assess the impact of vitD status on the severity of SARS-CoV-2 RI in adults. Material and Methods: A cross-sectional study that included adults infected with SARS-CoV-2 until 1/14/2020 was performed. Patients taking calcium, vitD supplementation or antiepileptics, with malabsorptive and/or calcium and phosphate metabolic disorders or stage 4 or 5 chronic kidney disease were excluded. Levels of 25-hydroxyvitamin D (25(OH)D) were obtained at the time of RI diagnosis. The participants were divided into 2 groups, depending on the vitD status (sufficiency and insufficiency [≥20 ng/mL]; deficiency [<20 ng/mL]), and in 3 groups of clinical severity of RI (adapted from the update [14/10/2020] of the standard 004/2020 of the Portuguese Directorate-General for Health): mild/moderate disease (g1); severe disease without bacterial coinfection (g2); severe disease with bacterial coinfection/critical disease (g3). Other factors associated with RI severity were analyzed. A multiple logistic regression model was developed to predict the severity of SARS-CoV-2 RI, considering vitD status as a categorical variable and other variables with statistical significance after univariate analysis. Results: This study encompassed 71 infected patients with a median age of 68 (p25;p75 = 58;77) years, 40 (56.3%) of which were women. 32 (45.1%) patients integrated g1, 14 (19.7%) g2 and 25 (35.2%) g3. 39 (54.9%) presented vitD deficiency and 32 (45.1%) vitD sufficiency or insufficiency. In the univariate analysis, vitD deficiency, age (>60 years old), male gender, Arterial Hypertension, Diabetes Mellitus, use of angiotensin-II receptor antagonist and reduced levels of ionized serum calcium correlated with the severity of RI. In the multivariate regression model that included these variables, vitD deficiency remained independently correlated with critical/severe disease with bacterial coinfection (g3 vs. g1: OR=9.7; CI95%=[1.7; 56.4]; p=0.011; g3 vs. g2: OR=6.3; CI95%=[1.1–37.0]; p=0.044), with a tendency, albeit not statistically significant, for severe RI without bacterial coinfection (g2 vs g1: OR=1.6; CI95%=[0.3; 7.4]; p=0.581). Conclusions: An independent association of vitD deficiency with the severity of SARS-CoV-2 RI was found, supporting the anti-inflammatory effects of vitD. It is essential to identify and treat its deficiency in patients prone to adverse outcomes of SARS-CoV-2 RI.